Institute of Nano Science and Technology, Habitat Centre, Phase - 10, Sector 64, Mohali, Punjab 160062, India.
Julia McFarlane Diabetes Research Centre (JMDRC), Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Biomater Adv. 2023 May;148:213383. doi: 10.1016/j.bioadv.2023.213383. Epub 2023 Mar 15.
Ulcerative colitis is a chronic inflammatory disease which poorly affects the colon and spreads toward the rectum over time. Cortisone (CRT) is a corticosteroid clinically used for the management of inflammatory diseases like colitis and other inflammatory bowel diseases. Due to some physicochemical properties' cortisone has limited potency in clinics. To overcome drug-related problems, we successfully prepared lipid nanocarriers with generally regarded as safe (GRAS) materials approved by USFDA. The present study aimed to assess the therapeutic efficacy of CRT-loaded 6-o-stearoyl ascorbic acid (SAA) nanostructured lipid carriers (NLCs) against DSS-induced colitis mice. Formulation and characterizations of reported nanostructured lipid carrier were performed according to our previously optimized parameters. The average hydrodynamic diameter of NLCs was 182 nm as measured by DLS with 81.14 % encapsulation efficacy. TEM, AFM and SEM images analysis confirmed its spherical appearance. hTERT-BJ cells viability up to a dose of 500 μg/ml shows cytocompatible characteristics of blank NLCs. CRT-loaded NLCs treatment normalizes physically observed parameters such as disease activity index, weight variation etc. These NLCs were able to significantly reduce the severity of colitis in terms of colon histoarchitecture, regaining of the goblet cells, mucins secretions, inhibition of proinflammatory cytokines etc. Treatment with CRT-loaded NLCs effectively downregulated the overexpression of inflammatory enzymes like cyclooxygenase-2 (COX-2), Inducible nitric oxide synthase (iNOS) etc. The results of this study concluded that these CRT-encapsulated NLCs efficiently manage the disease severity induced by DSS.
溃疡性结肠炎是一种慢性炎症性疾病，它会逐渐影响结肠并向直肠扩散。皮质醇（CRT）是一种临床上用于治疗结肠炎和其他炎症性肠病等炎症性疾病的皮质类固醇。由于皮质醇具有一些物理化学性质，其在临床上的效力有限。为了克服与药物相关的问题，我们成功地使用美国食品和药物管理局批准的一般认为安全（GRAS）材料制备了脂质纳米载体。本研究旨在评估负载 CRT 的 6-o-硬脂酰抗坏血酸（SAA）纳米结构化脂质载体（NLC）对 DSS 诱导的结肠炎小鼠的治疗效果。根据我们之前优化的参数，对报道的纳米结构化脂质载体进行了配方和特性研究。通过 DLS 测量，NLC 的平均水动力直径为 182nm，包封效率为 81.14%。TEM、AFM 和 SEM 图像分析证实了其球形外观。hTERT-BJ 细胞活力高达 500μg/ml 表明空白 NLC 具有细胞相容性。负载 CRT 的 NLC 治疗可使疾病活动指数、体重变化等观察到的生理参数正常化。这些 NLC 能够在结肠组织形态学、杯状细胞恢复、粘蛋白分泌、抑制促炎细胞因子等方面显著减轻结肠炎的严重程度。负载 CRT 的 NLC 治疗可有效下调炎症酶如环氧化酶-2（COX-2）、诱导型一氧化氮合酶（iNOS）等的过度表达。本研究的结果表明，这些包封 CRT 的 NLC 可有效控制 DSS 诱导的疾病严重程度。
